DESCRIPTION: (Applicant's Description) Chemotherapy remains one of the principal means of cancer treatment. Over the past 3 decades, this grant has allowed Memorial Hospital to rapidly test and apply new treatments to a variety of cancers. The overall goal of this project will be to conduct Phase I studies of new single agents and combination therapies developed at Memorial Hospital for application in disease specific Phase II and Phase III trials. Highest priority for new studies will be given to ideas and compounds developed within the Memorial Sloan Kettering Cancer Center for which we hold the IND. The clinical trials to be performed will include both molecular markers of response and pharmacokinetics when appropriate. All trials in this project are Phase I studies. The clinical trials performed in this project will be grouped into 3 specific aims. Specific aim 1 is the development of novel agents including geldanamycin analogs, 10 - propargyl-10 deazaaminopterin, arsenic trioxide, PS341, and desoxyepothilone B. Specific Aim Two is a target based therapy program utilizing Pyroxamide and is directed at the development of this putative differentiation agent. Finally, in Specific aim 3 correlative science is described to support these trials. Each of these clinical studies will be linked to pharmacokinetic and molecular laboratory correlative studies. Through this work, we expect to identify new, more active treatments for the successful management of human malignancies.